Objective To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherlands. Design Nationwide prospective cohort study. Setting All 118 hospitals in the Netherlands. Participants 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000. Main outcome measures Maternal, perinatal, and neonatal outcomes of pregnancy. Results 84% (n = 271) of the pregnancies were planned. Glycaemic control early in pregnancy was good in most women (HbA 1c ≤ 7.0% in 75% (n = 212) of the population), and folic acid supplementation was adequate in 70% (n = 226). 314 pregnancies that went beyond 24 weeks' gestation resulted in 324 infants. The rates of pre-eclampsia (40; 12.7%), preterm delivery (101; 32.2%), caesarean section (139; 44.3%), maternal mortality (2; 0.6%), congenital malformations (29; 8.8%), perinatal mortality (9; 2.8%), and macrosomia (146; 45.1%) were considerably higher than in the general population. Neonatal morbidity (one or more complications) was extremely high (260; 80.2%). The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies (4.2% (n = 11) v 12.2% (n = 6); relative risk 0.34, 95% confidence interval 0.13 to 0.88). Conclusion Despite a high frequency of planned pregnancies, resulting in overall good glycaemic control (early) in pregnancy and a high rate of adequate use of folic acid, maternal and perinatal complications were still increased in women with type 1 diabetes. Neonatal morbidity, especially hypoglycaemia, was also extremely high. Near optimal maternal glycaemic control (HbA 1c ≤ 7.0%) apparently is not good enough.

Objective To develop a clinical prediction rule that can help the clinician to identify women at high and low risk for gestational diabetes mellitus (GDM) early in pregnancy in order to improve the efficiency of GDM screening.Design We used data from a prospective cohort study to develop the clinical prediction rule.Setting The original cohort study was conducted in a university hospital in the Netherlands.Population Nine hundred and ninety-five consecutive pregnant women underwent screening for GDM.Methods Using multiple logistic regression analysis, we constructed a model to estimate the probability of development of GDM from the medical history and patient characteristics. Receiver operating characteristics analysis and calibration were used to assess the accuracy of the model.Main outcome measure The development of a clinical prediction rule for GDM. We also evaluated the potential of the prediction rule to improve the efficiency of GDM screening.Results The probability of the development of GDM could be predicted from the ethnicity, family history, history of GDM and body mass index. The model had an area under the receiver operating characteristic curve of 0.77 (95% CI 0.69-0.85) and calibration was good (Hosmer and Lemeshow test statistic, P = 0.25). If an oral glucose tolerance test was performed in all women with a predicted probability of 2% or more, 43% of all women would be tested and 75% of the women with GDM would be identified.Conclusions The use of a clinical prediction model is an accurate method to identify women at increased risk for GDM, and could be used to select women for additional testing for GDM.

OBJECTIVES -To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma during the first trimester of type 1 diabetic pregnancy and in the 4 months before gestation and to identify risk indicators predicting first trimester SH in a nonselected nationwide cohort of pregnant women with type 1 diabetes.RESEARCH DESIGN AND METHODS -We conducted a longitudinal cohort survey in 278 pregnant type 1 diabetic women using questionnaires at inclusion and at 17 weeks of gestation, addressing the frequencies of SH (i.e., external help required) and hypoglycemic coma, general characteristics, hypoglycemia awareness, blood glucose symptom threshold, and the Hypoglycemia Fear Survey.RESULTS -The occurrence of SH (including hypoglycemic coma) rose from 0.9 Ϯ 2.4 episodes per 4 months before gestation to 2.6 Ϯ 6.3 episodes during the first trimester (P Ͻ 0.001), including an increase in episodes of coma from 0.3 Ϯ 1.3 to 0.7 Ϯ 3.7 (P ϭ 0.03). The proportion of women affected by SH rose from 25 to 41% (P Ͻ 0.001). First-trimester SH was independently related to a history of SH before gestation (odds ratio CONCLUSIONS -In type 1 diabetic pregnancy, the risk of SH is increased already before pregnancy and rises further during the first trimester. A history of SH before gestation, longer duration of diabetes, an HbA 1c level Յ6.5%, and a higher total daily insulin dose were risk indicators predictive for SH during the first trimester. Further research should aim to elucidate how the benefits of strict glycemic control balance with the markedly increased risk of SH early in pregnancy.[ Diabetes Care 25:554 -559, 2002

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Context Non-alcoholic fatty liver disease (NAFLD) prevalence is high, especially in patients with obesity and type 2 diabetes, and is expected to rise steeply in the coming decades. Objective We estimated NAFLD prevalence in patients with type 1 diabetes and explored associated characteristics and outcomes. Data Sources We reviewed PubMed and Embase for studies on NAFLD and type 1 diabetes to March 2020. We screened references of included articles. Study Selection Two authors independently screened titles/abstracts. One author screened full text articles. NAFLD was defined as described in the individual studies, i.e. steatosis and/or fibrosis. Studies not reporting alternative causes of hepatic steatosis or only defining NAFLD as elevated liver enzymes, were excluded. Initially, 919 articles met selection criteria. Data extraction One researcher performed data extraction and risk of bias assessment using standardized tables. Data synthesis We assessed pooled prevalence rates by meta-analysis using a random-effects model, subsequently exploring heterogeneity by subgroup-, meta-regression-, and sensitivity analysis. Twenty studies between 2009 and 2019 were included (n=3901). Pooled NAFLD prevalence was 19.3% (95% CI 12.3-27.5%), increasing to 22.0% (95% CI 13.9-31.2%) in adults only. Pooled prevalence of ultrasound studies was high (27.1%, 95% CI 18.7-36.3%), compared to studies using magnetic resonance imaging (8.6%, 95% CI 2.1-18.6%), liver biopsy (19.3%, 95% CI 10.0-30.7%), or transient elastography (2.3%, 95% CI 0.6-4.8%). Conclusion NAFLD prevalence in patients with type 1 diabetes is considerable and is highly dependent on the specific diagnostic modality and NAFLD definition used. These data are helpful in directing actions to standardize NAFLD diagnosis, which will help defining contributing mechanisms and outcomes.

To establish whether insulin resistance and/or postprandial fatty acid metabolism might contribute to familial combined hyperlipidemia (FCH) we have examined parameters of insulin resistance and lipid metabolism in six FCH kindreds. Probands and relatives (n = 56) were divided into three tertiles on the basis of fasting plasma triglycerides (TG). Individuals in the highest tertile (TG > 2.5 mM; n = 14) were older and had increased body mass index, systolic blood pressure, and fasting plasma insulin concentrations compared with individuals in the lowest tertile (n = 24). The former also presented with decreased HDL cholesterol and increased total plasma cholesterol, HDL-TG, and apoprotein B, E, and CIII concentrations.Insulin concentrations were positively correlated with plasma apo B, apo CIII, apo E, and TG, and inversely with HDL cholesterol. Fasting nonesterified fatty acids (NEFA) were elevated in FCH subjects compared to six unrelated controls and five subjects with familial hypertriglyceridemia. Prolonged and exaggerated postprandial plasma NEFA concentrations were found in five hypertriglyceridemic FCH probands. In FCH the X2 minor allele of the AI-CIII-AIV gene cluster was associated with increased fasting plasma TG, apo CIII, apo AI, and NEFA concentrations and decreased postheparin lipolytic activities. The clustering of risk factors associated with insulin resistance in FCH indicates a common metabolic basis for the FCH phenotype and the syndrome of insulin resistance probably mediated by an impaired fatty acid metabolism. (J.

In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive disorder of phenylalanine metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH; EC 1.14.16.1). Cognitive problems, neuropsychological abnormalities and psychosocial problems have been reported frequently in children and adolescents with PKU, even in those who are treated early and continuously. However, the developmental consequences in adulthood of growing up with PKU are not well known. The aim of this study was to assess the course of life, sociodemographic outcomes and health-related quality of life in young adult patients with PKU identified on neonatal screening who were continuously on treatment. A total of 32 PKU patients 18 to 30 years old completed the Course of Life questionnaire, the RAND-36 Health Survey, and the cognitive scale of the TNO-AZL Adult Quality of Life (TAAQoL) questionnaire. The results of the Course of Life and Health-Related Quality of Life questionnaires were comparable to controls, except that a higher percentage received special education in primary school. Their educational attainment, however, was comparable to that of their peers. The results of this study demonstrate that although PKU is a chronic disease with the burden of strict dietary control, early and continuously treated patients with PKU can have a normal health-related quality of life and course of life.